The Expression Profiles of lncRNAs and Their Regulatory Network During Smek1/2 Knockout Mouse Neural Stem Cells Differentiation

2020 ◽  
Vol 15 (1) ◽  
pp. 77-88 ◽  
Author(s):  
Qichang Yang ◽  
Jing Wu ◽  
Jian Zhao ◽  
Tianyi Xu ◽  
Ping Han ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Wildtype Mouse ◽  
Pathway Network ◽  
Differentiation And Proliferation

Background: Previous studies indicated that the cell fate of neural stem cells (NSCs) after differentiation is determined by Smek1, one isoform of suppressor of Mek null (Smek). Smek deficiency prevents NSCs from differentiation, thus affects the development of nervous system. In recent years, lncRNAs have been found to participate in numerous developmental and biological pathways. However, the effects of knocking out Smek on the expression profiles of lncRNAs during the differentiation remain unknown. Objective: This study is to explore the expression profiles of lncRNAs and their possible function during the differentiation from Smek1/2 knockout NSCs. Methods: We obtained NSCs from the C57BL/6J mouse fetal cerebral cortex. One group of NSCs was from wildtype mouse (WT group), while another group was from knocked out Smek1/2 (KO group). Results: By analyzing the RNA-Seq data, we found that after knocking out Smek1/2, the expression profiles of mRNAs and lncRNAs revealed significant changes. Analyses indicated that these affected mRNAs have connections with the pathway network for the differentiation and proliferation of NSCs. Furthermore, we performed a co-expression network analysis on the differentially expressed mRNAs and lncRNAs, which helped reveal the possible regulatory rules of lncRNAs during the differentiation after knocking out Smek1/2. Conclusion: By comparing group WT with KO, we found 366 differentially expressed mRNAs and 12 lncRNAs. GO and KEGG enrichment analysis on these mRNAs suggested their relationships with differentiation and proliferation of NSCs. Some of these mRNAs and lncRNAs have been verified to play regulatory roles in nervous system. Analyses on the co-expression network also indicated the possible functions of affected mRNAs and lncRNAs during NSCs differentiation after knocking out Smek1/2.

scholarly journals Dissecting Hes-centered transcriptional networks in neural stem cell maintenance and tumorigenesis in Drosophila

2020 ◽  
Author(s):  
Srivathsa S. Magadi ◽  
Chrysanthi Voutyraki ◽  
Gerasimos Anagnostopoulos ◽  
Evanthia Zacharioudaki ◽  
Ioanna K. Poutakidou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Transcription Factor ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Asymmetric Cell Division ◽  
Transcriptional Networks ◽  
Malignant Tumours ◽  
Stem Cell Maintenance

ABSTRACTNeural stem cells divide during embryogenesis and post embryonic development to generate the entire complement of neurons and glia in the nervous system of vertebrates and invertebrates. Studies of the mechanisms controlling the fine balance between neural stem cells and more differentiated progenitors have shown that in every asymmetric cell division progenitors send a Delta-Notch signal back to their sibling stem cells. Here we show that excessive activation of Notch or overexpression of its direct targets of the Hes family causes stem-cell hyperplasias in the Drosophila larval central nervous system, which can progress to malignant tumours after allografting to adult hosts. We combined transcriptomic data from these hyperplasias with chromatin occupancy data for Dpn, a Hes transcription factor, to identify genes regulated by Hes factors in this process. We show that the Notch/Hes axis represses a cohort of transcription factor genes. These are excluded from the stem cells and promote early differentiation steps, most likely by preventing the reversion of immature progenitors to a stem-cell fate. Our results suggest that Notch signalling sets up a network of mutually repressing stemness and anti-stemness transcription factors, which include Hes proteins and Zfh1, respectively. This mutual repression ensures robust transition to neuronal and glial differentiation and its perturbation can lead to malignant transformation.

scholarly journals Drosophila as a Model for Developmental Biology: Stem Cell-Fate Decisions in the Developing Nervous System

2018 ◽  
Vol 6 (4) ◽  
pp. 25 ◽  
Author(s):  
Katherine Harding ◽  
Kristin White
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Cell Behavior ◽  
Stem Cell Fate ◽  
Cell Fate Decisions ◽  
Unique System ◽  
Developing Nervous System

Stem cells face a diversity of choices throughout their lives. At specific times, they may decide to initiate cell division, terminal differentiation, or apoptosis, or they may enter a quiescent non-proliferative state. Neural stem cells in the Drosophila central nervous system do all of these, at stereotypical times and anatomical positions during development. Distinct populations of neural stem cells offer a unique system to investigate the regulation of a particular stem cell behavior, while comparisons between populations can lead us to a broader understanding of stem cell identity. Drosophila is a well-described and genetically tractable model for studying fundamental stem cell behavior and the mechanisms that underlie cell-fate decisions. This review will focus on recent advances in our understanding of the factors that contribute to distinct stem cell-fate decisions within the context of the Drosophila nervous system.

scholarly journals Dissecting Hes-centred transcriptional networks in neural stem cell maintenance and tumorigenesis in Drosophila

Development ◽  
2020 ◽  
Vol 147 (22) ◽  
pp. dev191544
Author(s):  
Srivathsa S. Magadi ◽  
Chrysanthi Voutyraki ◽  
Gerasimos Anagnostopoulos ◽  
Evanthia Zacharioudaki ◽  
Ioanna K. Poutakidou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Transcription Factor ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Asymmetric Cell Division ◽  
Transcriptional Networks ◽  
Malignant Tumours ◽  
The Impact

ABSTRACTNeural stem cells divide during embryogenesis and juvenile life to generate the entire complement of neurons and glia in the nervous system of vertebrates and invertebrates. Studies of the mechanisms controlling the fine balance between neural stem cells and more differentiated progenitors have shown that, in every asymmetric cell division, progenitors send a Delta-Notch signal to their sibling stem cells. Here, we show that excessive activation of Notch or overexpression of its direct targets of the Hes family causes stem-cell hyperplasias in the Drosophila larval central nervous system, which can progress to malignant tumours after allografting to adult hosts. We combined transcriptomic data from these hyperplasias with chromatin occupancy data for Dpn, a Hes transcription factor, to identify genes regulated by Hes factors in this process. We show that the Notch/Hes axis represses a cohort of transcription factor genes. These are excluded from the stem cells and promote early differentiation steps, most likely by preventing the reversion of immature progenitors to a stem-cell fate. We describe the impact of two of these ‘anti-stemness’ factors, Zfh1 and Gcm, on Notch/Hes-triggered tumorigenesis.

scholarly journals LncRNA and mRNA Expression Profiles in Methylprednisolone Stimulated Neural Stem Cells

2021 ◽  
Vol 15 ◽  
Author(s):  
Yong Tang ◽  
Zhongyu Xie ◽  
Mengjun Ma ◽  
Kaidi Duan ◽  
Yuxi Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Mrna Expression ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Akt Signaling Pathway ◽  
External Stimulation ◽  
Cord Injury ◽  
And Migration ◽  
Insight Into

Spinal cord injury (SCI) is a devastating neurological disorder that affects thousands of individuals each year. Previously, our study in non-human primates with SCI demonstrated that methylprednisolone (MP) resulted in the dysfunction of neural stem cells (NSCs), which may help to explain the controversial roles of MP in SCI. However, the detailed mechanism is still unclear. In this manuscript, we investigated the LncRNA and mRNA expression profiles of NSCs treated with MP. A total of 63 differentially expressed LncRNAs and 174 differentially expressed mRNAs were identified. Gene ontology (GO) analysis showed that differentially expressed mRNAs were highly associated with terms related to regulation of external stimulation, secretion, and migration. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results indicated that the PI3K–Akt signaling pathway contributed to the functions of MP treated NSCs. Besides, 3899 co-expression pairs were constructed among the differentially expressed LncRNA and mRNA, among which five predicted target mRNAs with the differentially expressed LncRNAs were identified. These results provide greater insight into the precise mechanisms of MP mediating NSC dysfunction in SCI.

Neural Stem Cells to Glial Cells an Important Factor for Brain Injury

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Glial Cells ◽  
Brain Injuries ◽  
The Body ◽  
The Central Nervous System ◽  
Near Future

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.

scholarly journals Transcriptome Analysis of Eggplant Root in Response to Root-Knot Nematode Infection

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 470
Author(s):  
Min Zhang ◽  
Hongyuan Zhang ◽  
Jie Tan ◽  
Shuping Huang ◽  
Xia Chen ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Expression Profiles ◽  
Resistance Mechanism ◽  
Solanum Melongena ◽  
Enrichment Analysis ◽  
Nematode Resistance ◽  
Differentially Expressed ◽  
Root Knot Nematode ◽  
Solanum Torvum ◽  
Plant Nematode

Eggplant (Solanum melongena L.), which belongs to the Solanaceae family, is an important vegetable crop. However, its production is severely threatened by root-knot nematodes (RKNs) in many countries. Solanum torvum, a wild relative of eggplant, is employed worldwide as rootstock for eggplant cultivation due to its resistance to soil-borne diseases such as RKNs. In this study, to identify the RKN defense mechanisms, the transcriptomic profiles of eggplant and Solanum torvum were compared. A total of 5360 differentially expressed genes (DEGs) were identified for the response to RKN infection. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that these DEGs are mainly involved in the processes of response to stimulus, protein phosphorylation, hormone signal transduction, and plant-pathogen interaction pathways. Many phytohormone-related genes and transcription factors (MYB, WRKY, and NAC) were differentially expressed at the four time points (ck, 7, 14, and 28 days post-infection). The abscisic acid signaling pathway might be involved in plant-nematode interactions. qRT-PCR validated the expression levels of some of the DEGs in eggplant. These findings demonstrate the nematode-induced expression profiles and provide some insights into the nematode resistance mechanism in eggplant.

Human embryonic stem cells: challenges and opportunities

2006 ◽  
Vol 18 (8) ◽  
pp. 839 ◽  
Author(s):  
Steven L. Stice ◽  
Nolan L. Boyd ◽  
Sujoy K. Dhara ◽  
Brian A. Gerwe ◽  
David W. Machacek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Line ◽  
Cell Fate ◽  
Neural Development ◽  
Es Cells ◽  
Embryonic Stem ◽  
Normal Karyotype ◽  
Es Cell ◽  
Cell Therapies

Human and non-human primate embryonic stem (ES) cells are invaluable resources for developmental studies, pharmaceutical research and a better understanding of human disease and replacement therapies. In 1998, subsequent to the establishment of the first monkey ES cell line in 1995, the first human ES cell line was developed. Later, three of the National Institute of Health (NIH) lines (BG01, BG02 and BG03) were derived from embryos that would have been discarded because of their poor quality. A major challenge to research in this area is maintaining the unique characteristics and a normal karyotype in the NIH-registered human ES cell lines. A normal karyotype can be maintained under certain culture conditions. In addition, a major goal in stem cell research is to direct ES cells towards a limited cell fate, with research progressing towards the derivation of a variety of cell types. We and others have built on findings in vertebrate (frog, chicken and mouse) neural development and from mouse ES cell research to derive neural stem cells from human ES cells. We have directed these derived human neural stem cells to differentiate into motoneurons using a combination of developmental cues (growth factors) that are spatially and temporally defined. These and other human ES cell derivatives will be used to screen new compounds and develop innovative cell therapies for degenerative diseases.

scholarly journals PTMAc-PEG-PTMAc hydrogel modified by RGDC and hyaluronic acid promotes neural stem cells' survival and differentiation in vitro

RSC Advances ◽  
2017 ◽  
Vol 7 (65) ◽  
pp. 41098-41104 ◽  
Author(s):  
Ruirui Yang ◽  
Caixia Xu ◽  
Tao Wang ◽  
Yuanqi Wang ◽  
Jingnan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Hyaluronic Acid ◽  
Neural Stem Cells ◽  
Biological Properties ◽  
Central Nervous System Injury ◽  
Bioactive Molecules

The enhancement of the biological properties of hydrogels by surface modifying with bioactive molecules is of great significance, especially for the treatment of central nervous system injury by combining engrafted cells.

scholarly journals Bioinformatics-Based Study to Investigate Potential Differentially Expressed Genes and miRNAs in Hashimoto’s Thyroiditis

2021 ◽  
Author(s):  
Li Guoquan ◽  
Du Junwei ◽  
He Qi ◽  
Fu Xinghao ◽  
Ji Feihong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Treatment Options ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Chronic Lymphocytic Thyroiditis ◽  
Hub Genes

Abstract BackgroundHashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a common autoimmune disease, which mainly occurs in women. The early manifestation was hyperthyroidism, however, hypothyroidism may occur if HT was not controlled for a long time. Numerous studies have shown that multiple factors, including genetic, environmental, and autoimmune factors, were involved in the pathogenesis of the disease, but the exact mechanisms were not yet clear. The aim of this study was to identify differentially expressed genes (DEGs) by comprehensive analysis and to provide specific insights into HT. MethodsTwo gene expression profiles (GSE6339, GSE138198) about HT were downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were assessed between the HT and normal groups using the GEO2R. The DEGs were then sent to the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were discovered using Cytoscape and CytoHubba. Finally, NetworkAnalyst was utilized to create the hub genes' targeted microRNAs (miRNAs). ResultsA total of 62 DEGs were discovered, including 60 up-regulated and 2 down-regulated DEGs. The signaling pathways were mainly engaged in cytokine interaction and cytotoxicity, and the DEGs were mostly enriched in immunological and inflammatory responses. IL2RA, CXCL9, IL10RA, CCL3, CCL4, CCL2, STAT1, CD4, CSF1R, and ITGAX were chosen as hub genes based on the results of the protein-protein interaction (PPI) network and CytoHubba. Five miRNAs, including mir-24-3p, mir-223-3p, mir-155-5p, mir-34a-5p, mir-26b-5p, and mir-6499-3p, were suggested as likely important miRNAs in HT. ConclusionsThese hub genes, pathways and miRNAs contribute to a better understanding of the pathophysiology of HT and offer potential treatment options for HT.

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